Investigators from Case Western Reserve and Makerere University are conducting a multifaceted study of HIV infection in Uganda, funded by ICAR International Collaboration for AIDS Research). A component of that study addresses the materno-fetal/newborn transmission of HIV, and our proposal deals with the placental aspects of this form of transmission. The placenta has many physiological functions, including protection of the fetus from maternal infections, probably through humoral secretions and cellular responses. The pattern of these responses provides a clue to the type of microorganism involved and its portal of entry. Acute inflammation of placental membranes (chorioamnionitis) is associated with bacterial infections, whereas chronic placental villous inflammation (villitis) is particularly associated with viral infections. The goal of our add-on study is to gain better understanding of the mechanisms of materno-fetal transmission by the examination of 200 placentas each from HIV seropositive and seronegative women included in the ICAR project. Coded placentas will be sampled and processed according to protocol. Histological sections will be stained for pathologic studies and for bacteria, spirochetes, fungi and mycobacteria. Using immunocytochemical methods, antigens of HIV, malaria, Herpes simplex, virus, cytomegalovirus and Hepatitis B will be sought in defined placental sites. In-situ hybridization will be used additionally for HIV detection. These findings will be correlated with data from the ICAR project: virologic, and immunologic studies of the mother's cord and infant's blood and clinical course of the mother and infant. It is postulated that a significantly higher frequency of chronic villitis with positive detection of HIV in the placentas of HIV+ patients will support a transplacental mechanism of materno-fetal HIV transmission. This information may guide obstetric and perinatal management and may be predictive of the infant's future clinical course.